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International Journal of Cancer May 2020Smoking is indisputably linked to lung cancer, yet only a small fraction of smokers develops this disease. Although previously tobacco-derived carcinogens and enzyme... (Review)
Review
Smoking is indisputably linked to lung cancer, yet only a small fraction of smokers develops this disease. Although previously tobacco-derived carcinogens and enzyme polymorphisms have been identified to increase the risk for smokers, recent epidemiological data suggest even sex-specificity as a new and additional factor. Obviously, women have a higher risk to develop lung cancer upon smoking than men. Overall, the odds ratio to develop lung cancer was almost three times greater for women than for men, DNA adduct levels were higher among females than in males and mutations in the tumor suppressor gene p53 and the proto-oncogene K-RAS were more frequently found in women than in men. A growing number of studies suggest that the interaction between tobacco carcinogens and endogenous and exogenous sex steroids may be important. Women taking hormone replacement therapy (HRT) or oral contraceptives experienced to have an increased lung cancer incidence. Epidemiologic data on HRT show a significant association between both a younger median age at lung cancer diagnosis and a shorter median survival time. Another clue is the significantly higher number of lung cancer diagnosed women who are largely premenopausal in comparison to diagnosed men in the same age or women with shorter menstrual cycles. Finally, the Coronary Drug Project (men who received estrogen preparations to reduce future cardiac events) was stopped when increased lung cancer mortality was observed in the estrogen therapy group. The present review provides a short overview and discussion on lung cancer risk and the impact thereon of sex.
Topics: Carcinogens; Female; Hormone Replacement Therapy; Humans; Incidence; Lung Neoplasms; Male; Proto-Oncogene Mas; Proto-Oncogenes; Risk Factors; Sex Factors; United States
PubMed: 31583690
DOI: 10.1002/ijc.32716 -
Oncogene Apr 2021More than 25 years of research and preclinical validation have defined EphA2 receptor tyrosine kinase as a promising molecular target for clinical translation in cancer... (Review)
Review
More than 25 years of research and preclinical validation have defined EphA2 receptor tyrosine kinase as a promising molecular target for clinical translation in cancer treatment. Molecular, genetic, biochemical, and pharmacological targeting strategies have been extensively tested in vitro and in vivo, and drugs like dasatinib, initially designed to target SRC family kinases, have been found to also target EphA2 activity. Other small molecules, therapeutic targeting antibodies, and peptide-drug conjugates are being tested, and more recently, approaches harnessing antitumor immunity against EphA2-expressing cancer cells have emerged as a promising strategy. This review will summarize preclinical studies supporting the oncogenic role of EphA2 in breast cancer, lung cancer, glioblastoma, and melanoma, while delineating the differing roles of canonical and noncanonical EphA2 signaling in each setting. This review also summarizes completed and ongoing clinical trials, highlighting the promise and challenges of targeting EphA2 in cancer.
Topics: Humans; Neoplasms; Oncogenes; Receptor, EphA2
PubMed: 33686241
DOI: 10.1038/s41388-021-01714-8 -
Experimental Hematology Oct 2022Dysregulation of transcription factor genes represents a unique molecular etiology of hematological malignancies. A number of transcription factors that play a role in... (Review)
Review
Dysregulation of transcription factor genes represents a unique molecular etiology of hematological malignancies. A number of transcription factors that play a role in hematopoietic cell development, lymphocyte activation, or their maintenance have been identified as oncogenes or tumor suppressors. Many of them exert oncogenic abilities in a context-dependent manner by governing the key transcriptional program unique to each cell type. IRF4, a member of the interferon regulatory factor (IRF) family, acts as an essential regulator of the immune system and is a prime example of a stage-specific oncogene. The expression and oncogenicity of IRF4 are restricted to mature lymphoid neoplasms, while IRF4 potentially serves as a tumor suppressor in other cellular contexts. This is in marked contrast to its immediate downstream target, MYC, which can cause cancers in a variety of tissues. In this review article, we provide an overview of the roles of IRF4 in the development of the normal immune system and lymphoid neoplasms and discuss the potential mechanisms of lineage- and stage-specific oncogenicity of IRF4.
Topics: Cell Differentiation; Hematopoiesis; Interferon Regulatory Factors; Lymphocyte Activation; Oncogenes
PubMed: 35908629
DOI: 10.1016/j.exphem.2022.07.300 -
Cancer Science Feb 2021Recent studies of the cancer genome have identified numerous patients harboring multiple mutations (MM) within individual oncogenes. These MM (de novo MM) in cis... (Review)
Review
Recent studies of the cancer genome have identified numerous patients harboring multiple mutations (MM) within individual oncogenes. These MM (de novo MM) in cis synergistically activate the mutated oncogene and promote tumorigenesis, indicating a positive epistatic interaction between mutations. The relatively frequent de novo MM suggest that intramolecular positive epistasis is widespread in oncogenes. Studies also suggest that negative and higher-order epistasis affects de novo MM. Comparison of de novo MM and MM associated with drug-resistant secondary mutations (secondary MM) revealed several similarities with respect to allelic configuration, mutational selection and functionality of individual mutations. Conversely, they have several differences, most notably the difference in drug sensitivities. Secondary MM usually confer resistance to molecularly targeted therapies, whereas several de novo MM are associated with increased sensitivity, implying that both can be useful as therapeutic biomarkers. Unlike secondary MM in which specific secondary resistant mutations are selected, minor (infrequent) functionally weak mutations are convergently selected in de novo MM, which may provide an explanation as to why such mutations accumulate in cancer. The third type of MM is MM from different subclones. This type of MM is associated with parallel evolution, which may contribute to relapse and treatment failure. Collectively, MM within individual oncogenes are diverse, but all types of MM are associated with cancer evolution and therapeutic response. Further evaluation of oncogenic MM is warranted to gain a deeper understanding of cancer genetics and evolution.
Topics: Carcinogenesis; Humans; Mutation; Neoplasms; Oncogenes
PubMed: 33073435
DOI: 10.1111/cas.14699 -
Report on Carcinogens : Carcinogen... 2011
Topics: Acrylamide; Animals; Carcinogens; Humans; Neoplasms
PubMed: 21829240
DOI: No ID Found -
IARC Monographs on the Evaluation of... 1999
Topics: Animals; Carbazoles; Carcinogenicity Tests; Carcinogens; Humans; Neoplasms, Experimental
PubMed: 10476405
DOI: No ID Found -
IARC Monographs on the Evaluation of... 1999
Topics: Animals; Carcinogenicity Tests; Carcinogens; Chlorofluorocarbons, Methane; Humans; Mutagenicity Tests; Mutagens; Neoplasms, Experimental
PubMed: 10476408
DOI: No ID Found -
IARC Monographs on the Evaluation of... 1999
Topics: Carcinogenicity Tests; Carcinogens; Humans; Hydrazines; Mutagenicity Tests; Mutagens; Neoplasms, Experimental; Salmonella typhimurium
PubMed: 10476419
DOI: No ID Found -
Oncogene Feb 2022Thirteen percent of cancers worldwide are associated with viral infections. While many human oncogenic viruses are widely endemic, very few infected individuals develop... (Review)
Review
Thirteen percent of cancers worldwide are associated with viral infections. While many human oncogenic viruses are widely endemic, very few infected individuals develop cancer. This raises the question why oncogenic viruses encode viral oncogenes if they can replicate and spread between human hosts without causing cancer. Interestingly, viral infection triggers innate immune signaling pathways that in turn activate tumor suppressors such as p53, suggesting that tumor suppressors may have evolved not primarily to prevent cancer, but to thwart viral infection. Here, we summarize and compare several major immune evasion strategies used by viral and non-viral cancers, with a focus on oncogenes that play dual roles in promoting tumorigenicity and immune evasion. By highlighting important and illustrative examples of how oncogenic viruses evade the immune system, we aim to shed light on how non-viral cancers avoid immune detection. Further study and understanding of how viral and non-viral oncogenes impact immune function could lead to improved strategies to combine molecular therapies targeting oncoproteins in combination with immunomodulators.
Topics: Oncogenes
PubMed: 35022539
DOI: 10.1038/s41388-021-02145-1 -
Nature Materials Jul 2020Defining the interplay between the genetic events and microenvironmental contexts necessary to initiate tumorigenesis in normal cells is a central endeavour in cancer...
Defining the interplay between the genetic events and microenvironmental contexts necessary to initiate tumorigenesis in normal cells is a central endeavour in cancer biology. We found that receptor tyrosine kinase (RTK)-Ras oncogenes reprogram normal, freshly explanted primary mouse and human cells into tumour precursors, in a process requiring increased force transmission between oncogene-expressing cells and their surrounding extracellular matrix. Microenvironments approximating the normal softness of healthy tissues, or blunting cellular mechanotransduction, prevent oncogene-mediated cell reprogramming and tumour emergence. However, RTK-Ras oncogenes empower a disproportional cellular response to the mechanical properties of the cell's environment, such that when cells experience even subtle supra-physiological extracellular-matrix rigidity they are converted into tumour-initiating cells. These regulations rely on YAP/TAZ mechanotransduction, and YAP/TAZ target genes account for a large fraction of the transcriptional responses downstream of oncogenic signalling. This work lays the groundwork for exploiting oncogenic mechanosignalling as a vulnerability at the onset of tumorigenesis, including tumour prevention strategies.
Topics: Animals; Biomechanical Phenomena; Cell Line, Tumor; Cellular Reprogramming; Extracellular Matrix; Female; Gene Expression Regulation; Humans; Mammary Glands, Human; Mice; Mice, Inbred Strains; Mice, Knockout; Microscopy; Oncogenes; Pancreas; Sequence Analysis, RNA
PubMed: 32066931
DOI: 10.1038/s41563-020-0615-x